Abstract Sickle cell disease (SCD), an inherited disorder of the red blood cell characterized by vasocclusive episodes of acute pain (VOE), which may progress to chronic persistent pain with increasing morbidity, impaired quality of life, health care utilization, costs of care, and risk of premature mortality. Thus, the relief of pain is an important therapeutic target in interventional clinical trials in SCD. Direct measures of patient reported pain experience, without interpretation by a clinician or anyone else are important for both for determining eligibility and as endpoints in clinical trials. Lacking validated direct measures of cognitive and affective domains of pain, clinical trials have relied on surrogate measures such as the frequency of healthcare utilization in the emergency departments or hospital, or readiness for discharge from hospital following treatment of VOE. There is a clear and urgent need for a valid, reliable, measure in the patient's voice of both cognitive as well as affective domains of pain, which detects clinically meaningful change and can parallel or complement traditional measures of efficacy. We have developed and electronic pain diary for SCD with input from the literature, expert and members of the target population and have described the development and content validity, preliminary user review, and low burden of use of this web-based multidimensional pain diary in adolescents with SCD. Our overarching objective is to provide SCD clinical researchers a reliable, and valid electronically administered multi-dimensional measure of pain intensity and pain interference which can detect clinically important change in children, adolescents and young adults. To achieve this objective, we propose the following specific aims: Aim 1. To extend content validity of the electronic pain diary in patients ? 8 years through young adulthood through additional user input for establishing face validity, user understanding, and usability. We seek user input in item generation in up to 30 patients each in the age groups of 8-12,13-18 and >18 years till we reach thematic saturation, followed by cognitive interviews to demonstrate user understanding and usability. In a prospective observational study, we will capture daily pain diary, Brief pain inventory short form, patient general impression of change and PROMIS profile during steady state, the course of a VOE and in the recovery phase to study aims 2-4. Aim 2. To establish the reliability of electronic pain diary. We will evaluate the internal consistency and test-retest reliability of the electronic pain diary in children, adolescents and adult patients with SCD. Aim 3. To establish the validity of the electronic pain diary. We will test the convergent and divergent validity in the steady state phase. Aim 4. To establish the responsiveness of the electronic pain diary. We will test the ability of the electronic pain diary to detect minimal important change in pain intensity and interference following VOE. The completion of these aims is likely to lead to the development of a final package for submission to the FDA for qualification of pain intensity and pain interference as an endpoint in clinical trials and optimize drug development.